Abstract
In recent years, there has been an upsurge of interest in identifying women with genetic predisposition and this has been facilitated by enhanced understanding of the genetic basis for breast cancer susceptibility derived from genome-wide linkage analysis and mutational screening. The focus has shifted from high-penetrance genes to intermediate and low penetrance mutations that confer lower levels of risk individually but collectively are more significant. There has been frenzied public interest in genetic testing and risk reduction strategies following revelations in the New York Times in May 2013 that the famed actress Angelina Jolie had chosen to undergo bilateral prophylactic mastectomy due to carriage of a BRCA-1 gene mutation. Genetic counseling and testing for breast cancer predisposition have been formally implemented in many countries, and the number of women seeking genetic testing continues to rise. Nonetheless, despite these advances in genetics, approximately 30% of familial breast cancer risk remains unaccounted for by mutations in currently known genes. Moreover, genetic changes do not necessarily have a causative association with a diseased state, and phenotypic manifestations of cancer are variable. The clinical management of women with an asymptomatic mutation in BRCA1 and BRCA2 or carriage of a mutation in other high-risk genes such as TP53, PALB2, or pTEN is increasingly complex. Approaches include screening, chemoprevention, and risk-reducing surgery but the outcomes of these different interventions for risk reduction remain variable in terms of accuracy of data and levels of certainty. In particular, although an intervention may reduce the chance of developing breast cancer, this may not translate into a reduction in mortality with gains in both breast cancer-specific and overall survival. No randomized trials have addressed the impact of these risk-reducing strategies on either incidence or survival outcomes with much of the evidence for efficacy derived from observational studies that are prone to systematic biases. It important that women with a hereditary predisposition are fully informed about the limitations of the existing knowledge base relating to risk-reducing interventions for breast cancer.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- BPM:
-
Bilateral prophylactic mastectomy
- BSO:
-
Bilateral salpingo-oophorectomy
- ER:
-
Estrogen receptor
- HER2:
-
Human epidermal growth factor receptor
- HRT:
-
Hormone replacement therapy
- MRI:
-
Magnetic resonance imaging
- NICE:
-
National Institute for Health and Clinical Excellence
- PR:
-
Progesterone receptor
- TNBC:
-
Triple negative breast cancer
- VUS:
-
Variations of uncertain clinical significance
References
Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28(2):232–9.
Mcpherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 2000;321(7261):624–8.
Oseni T, Jatoi I. An overview of the role of prophylactic surgery in the management of individuals with a hereditary cancer predisposition. Surg Clin North Am. 2008;88(4):739–58.
Jatoi I, Benson JR, Liau SS, et al. The role of surgery in cancer prevention. Curr Probl Surg. 2010;47(10):750–830.
Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC. Early breast cancer. Lancet. 2009;373(9673):1463–79.
Harvie M, Howell A, Evans DG. Can diet and lifestyle prevent breast cancer: what is the evidence? Am Soc Clin Oncol Educ Book. 2015;2015:e66–73.
Gabai-Kapara E, Lahad A, Kaufman B, et al. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci U S A. 2014;111(39):14205–10.
Hartmann LC, Lindor NM. The role of risk-reducing surgery in hereditary breast and ovarian cancer. N Engl J Med. 2016;374(5):454–68.
Narod SA, Amos C. Estimating the power of linkage analysis in hereditary breast cancer. Am J Hum Genet. 1990;46(2):266–72.
Knudson AG Jr. Hereditary cancer, oncogenes and anti-oncogenes. Cancer Res. 1985;45(5):1437–43.
Knudson AG Jr. Genetics of human cancer. Annu Rev Genet. 1986;20:231–51.
King MC, Levy-Lahad E, Lahad A. Population-based screening for BRCA1 and BRCA2: 2014 Lasker award. JAMA. 2014;312(11):1091–2.
King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302(5645):643–6.
Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;226(20):1401–8.
Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet. 1998;62(3):676–89.
Satagopan JM, Boyd J, Kauff ND, et al. Ovarian cancer risk in Askenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res. 2002;8(12):3776–81.
Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371(6):497–506.
Eisen A, Lubinski J, Klijn J, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol. 2005;23(30):7491–6.
Antoniou A, Cunningham A, Peto J, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 2008;98:1457–66. https://doi.org/10.1038/sj.bjc.6604305.
Hutchinson L. Screening: BRCA testing in women younger than 50 with triple-negative breast cancer is cost effective. Nat Rev Clin Oncol. 2010;7(11):611.
Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol. 2010;4(3):174–91.
Lane DP, Hupp TR. Drug discovery and p53. Drug Discov Today. 2003;8(8):347–55.
Bougeard G, Renaux-Petel M, Flaman JM, et al. Revisiting li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol. 2015;33(21):2345–52.
Nelen MR, Padberg GW, Peeters EA, et al. Localization of the gene for Cowden disease to chromosome 10q22–23. Nat Genet. 1996;13(1):114–6.
Thompson D, Easton D. The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia. 2004;9(3):221–36.
Antoniou AC, Easton DF. Models of genetic susceptibility to breast cancer. Oncogene. 2006;25(43):5898–905.
Udler MS, Meyer KB, Pooley KA, et al. FGFR2 variants and breast cancer risk: ne-scale mapping using African American studies and analysis of chromatin conformation. Hum Mol Genet. 2009;18(9):1692–703.
Meijers-Heijboer H, Van Den Ouweland A, Klijn J, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31(1):55–9.
Geller G, Bernhardt BA, Doksum T, Helzlsouer KJ, Wilcox P, Holtzman NA. Decision-making about breast cancer susceptibility testing: how similar are the attitudes of physicians, nurse practitioners, and at-risk women? J Clin Oncol. 1998;16(8):2868–76.
National Collaborating Centre for Cancer. Familial breast cancer: classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer, NICE Clinical Guidelines, No. 164. Cardiff, UK: National Collaborating Centre for Cancer; 2013.
Metcalf K, An E, Senter L, et al. International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer. 2019;121:15–21.
Black WC, Nease RF Jr, Tosteson AN. Perceptions of breast cancer risk and screening effectiveness in women younger than 50 years of age. J Natl Cancer Inst. 1995;87(10):720–31.
Amir E, Freedman OC, Seruga B, Evans DG. Assessing women at high risk of breast cancer: a review of risk assessment models. J Natl Cancer Inst. 2010;102(10):680–91.
Pijpe A, Andrieu N, Easton DF, et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD- RISK). BMJ. 2012;345:e5660.
Kuhl C, Weigel S, Schrading S, et al. Prospective multicenter cohort study to re ne management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J Clin Oncol. 2010;28(9):1450–7.
Chang-Claude J, Andrieu N, Rookus M, et al. Age at menarche and menopause and breast cancer risk in the international BRCA1/2 carrier cohort study. Cancer Epidemiol Biomark Prev. 2007;16(4):740–6.
Kauff N, Domchek S, Friebel T, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1 and BRCA2 associated breast and gynaecologic cancer: a multicentre, prospective study. J Clin Oncol. 2008;26(8):1331–7.
Heemskerk-Gerritsen BAM, Menke-Pluijmers MBE, Jager A, et al. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BCA1 and BRCA2 mutation carriers: a prospective analysis. Ann Oncol. 2013;24(8):2029–35.
Visvanathan K, Chlebowski RT, Hurley P, et al. American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. 2009;27(19):3235–58.
King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and bowel project (NSABP-P1) breast cancer prevention trial. JAMA. 2001;286(18):2251–6.
Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med. 1999;340(2):77–84.
Rebbeck TR, Freibel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE study group. J Clin Oncol. 2004;22(6):1055–62.
Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346(21):1609–15.
Domchek SM, Friebel TM, Neuhausen SL, et al. Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol. 2006;7(3):223–9.
Klaren HM, van’t Veer LJ, van Leeuwen FE, Rookus MA. Potential for bias in studies on efficacy of prophylactic surgery for BRCA1 and BRCA2 mutation. J Natl Cancer Inst. 2003;95(13):941–7.
Hartmann LC, Degnim A, Schaid DJ. Prophylactic mastectomy for BRCA1/2 carriers; progress and more questions. J Clin Oncol. 2004;22(6):981–3.
Lakhani SR, Van de Vijver MJ, Jacquemier J, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER2 and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol. 2002;20(9):2310–8.
Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967–75.
Eleje GU, et al. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev. 2018;8(8):CD012464.
Heemskerk-Gerritsen BAM, Jager A, Koppert LB, et al. Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2019;177(3):723–33.
Giannakeas V, Narod SA. The expected benefit of preventive mastectomy on breast cancer incidence and mortality in BRCA mutation carriers, by age at mastectomy. Breast Cancer Res Treat. 2018;167:263–7.
Carbine NE, Lostumbo L, Wallace J, et al. Risk-reducing mastectomy for the prevention of primary breast cancer. Cochrane Database Syst Rev. 2018;4:CD002748.
Montgomery LL, Tran KN, Borgen P, et al. Issues of regret in women with contralateral prophylactic mastectomies. Ann Surg Oncol. 1999;6:546–52.
Jatoi I. Bilateral mastectomy for unilateral breast cancer: a perplexing trend. Indian J Surg Oncol. 2015;6(4):387–9.
Van den Broek AJ, van’t Veer LJ, Hooning MJ, et al. Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. J Clin Oncol. 2016;34(5):409–18.
Van Sprundel TC, Schmidt MK, Rookus MA, et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or 71 BRCA2 mutation carriers. Br J Cancer. 2005;93(3):287–92.
Benson JR, Winters ZE. Contralateral prophylactic mastectomy. Br J Surg. 2016;103(10):1249–50. https://doi.org/10.1002/bjs.10223.
Jatoi I. Options in breast cancer local therapy: who gets what? World J Surg. 2012;36(7):1498–502.
Chadab TM, Bernstein J, Lifrieri A, et al. Is it worth the risk? Contralateral prophylactic mastectomy with immediate bilateral breast reconstruction. Ann Plast Surg. 2021;87(Suppl. 1):S2–6.
Mallon P, Feron JG, Couturaud B, et al. The role of nipple-sparing mastectomy in breast cancer: a comprehensive review of the literature. Plast Reconstr Surg. 2013;131(5):969–84.
Murthy V, Chamberlain RS. Nipple-sparing mastectomy in modern breast practice. Clin Anat. 2013;26(1):56–65.
Jakub JW, Peled AW, Gray RJ, et al. Oncologic safety of prophylactic nipple-sparing mastectomy in a population with BRCA mutations: a multi-institutional study. JAMA Surg. 2018;15(2):123–9.
Nagaraja V, Edirimanne S, Eslick GD, et al. Is sentinel lymph node biopsy necessary in patients undergoing prophylactic mastectomy? A systematic review and meta-analysis. Breast J. 2016;22:158–65.
Boughey JC, Khakpour N, Meric-Bernstam F, et al. Selective use of sentinel lymph node surgery during prophylactic mastectomy. Cancer. 2006;107:1440–7. https://doi.org/10.1002/cncr.22176.
Murthy V, Chamberlain RS. Prophylactic mastectomy in patients at high risk: is there a role for sentinel lymph node biopsy? Clin Breast Cancer. 2013;13:180–7. https://doi.org/10.1016/j.clbc.2012.12.001.
DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14:500–15. https://doi.org/10.1016/S1470-2045(13)70076-7.
Agha RA, Wellstead G, Sagoo H, et al. Nipple sparing versus skin sparing mastectomy: a systematic review protocol. BMJ Open 6(5), e010151 (2016). The role of mammography and ultrasound regardless of patient mutation status, age, and breast density. J Clin Oncol. 2015;33(10):1128–35.
Moreno L, Linossi C, Esteban I, et al. Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics. Clin Transl Oncol. 2016;18(10):981–7. https://doi.org/10.1007/s12094-015-1470-0.
Jatoi I, Benson JR. Management of patients with a hereditary predisposition for breast cancer. Future Oncol. 2016;12(19):2277–88. https://doi.org/10.2217/fon-2016-0186.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Benson, J.R., Muktar, S., Jatoi, I. (2023). Risk-Reducing Surgery for Breast Cancer. In: Toi, M. (eds) Screening and Risk Reduction Strategies for Breast Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-19-7630-8_7
Download citation
DOI: https://doi.org/10.1007/978-981-19-7630-8_7
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-19-7629-2
Online ISBN: 978-981-19-7630-8
eBook Packages: MedicineMedicine (R0)